Standard Proton Pump Inhibitor Research Articles

Evolution of the use, effectiveness and safety of bismuth-containing quadruple therapy for Helicobacter pylori infection between 2013 and 2021: results from the European registry on H. pylori management (Hp-EuReg)

BackgroundBismuth quadruple therapies (BQTs) including bismuth, a proton pump inhibitor (PPI) and two antibiotics have been shown to be highly effective for treating Helicobacter pylori infection even in areas of...

Efficacy of Vonoprazan 10 mg and 20 mg for Patients With Proton Pump Inhibitor-Refractory Functional Dyspepsia: A Double-Blinded, Randomized Study.

A proportion of patients with functional dyspepsia (FD) have inadequate symptom control with proton pump inhibitors (PPIs) treatment. Vonoprazan demonstrates higher efficacy in acid reduction than PPI; however, the existing efficacy data for vonoprazan in treating PPI-refractory FD is limited. This double-blinded, randomized controlled trial study was conducted at Rajavithi Hospital, Bangkok between December 2022 and 2023. Patients with FD who were unresponsive to the standard dose PPI were randomly assigned (1:1) to receive either 10 mg or 20 mg of vonoprazan for a 4-week duration, with a subsequent 4-week follow-up after treatment. The primary outcome was changes in the Global Overall Symptoms Scale (GOSS). Sixty patients were randomized without significant differences in baseline characteristics between both groups. The mean GOSS between the 10-mg vonoprazan and the 20-mg vonoprazan arm were 25.73 and 26.17 at week 0, 14.33 and 15.50 at week 2, 9.37 and 10.04 at week 4, and 9.79 and 9.33 at week 8, respectively (all p < 0.001 vs. baseline and p > 0.05 between groups). The quality of life was improved, with the Nepean dyspepsia index changing -4.13 and -4.25 at week 4, respectively (all p < 0.001 vs. baseline; p = 0.853 between groups). Symptom response rates (> 50% improvement in GOSS) were 72.4% and 75.9% at week 8, respectively (p = 0.24 between groups). No serious adverse events were observed. Vonoprazan demonstrated significant effects in the alleviation of symptoms in PPI-refractory FD patients. There was no statistically significant difference in symptom alleviation between the 10 mg and 20 mg doses of vonoprazan.

Twice-Daily Proton Pump Inhibitor Induces Higher Remission Rate in Eosinophilic Esophagitis Than Once-Daily Regimen Regardless of Total Daily Dose.

The optimal proton pump inhibitor (PPI) regimen for eosinophilic esophagitis (EoE) is unclear. We compared histologic response rates of different dosing combinations. A total of 305 patients with newly diagnosed EoE received standard (omeprazole 20 mg daily), once-daily moderate (40 mg daily), twice-daily moderate (20 mg twice daily), or high (40 mg twice daily) dose PPI for ≥8 weeks. Approximately 42.3% achieved histologic response to PPI, with higher rates for twice-daily (moderate 52.8%/high 54.3%) than once-daily (standard 11.8%/moderate 10%) dosing ( P < 0.0001). On multivariable analysis, twice-daily moderate (adjusted odds ratio 6.75, confidence interval 2.53-18.0, P = 0.0008) and high (adjusted odds ratio 12.8, confidence interval 4.69-34.8, P < 0.0001) doses independently predicted histologic response. Twice-daily PPI is associated with higher EoE histologic response rates than once-daily regimen.

Potassium-competitive acid blockers and proton-pump inhibitors for healing of erosive esophagitis: a systematic review and network meta-analysis.

Proton-pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) are recommended for erosive esophagitis (EE), with good safety and tolerance. However, it is unclear which is the best treatment option for EE. This study aimed to evaluate the comparative efficacy of P-CABs and PPIs for healing EE patients, seeking an appropriate treatment choice in the 4- or 8-week treatment and standard or double dose. A systematic review and network meta-analysis. Relevant databases were searched to collect randomized controlled trials of PPIs and P-CABs in the treatment of EE up to 31 May 2023. Studies on standard or double-dose PPIs or P-CABs which were published in English and assessed 4- or 8-week healing effects in EE were included. A network meta-analysis was performed to evaluate the efficacy of the treatments under the frequentist framework. Sensitivity and subgroup analyses of patients with different baseline EE were also conducted. In all, 34 studies involving 25,054 patients and 9 PPIs, 6 P-CABs, or placebo treatment interventions were included. The pooled 4-week healing rate was significantly statistically lower than the pooled 8-week healing rate for most treatments. Besides, the higher healing rate of double-dose treatment than standard-dose treatment was not observed in the initial treatment of most drugs. The main analysis only included studies conducted for both patients with and without severe EE at baseline, and the proportion of severe EE included in the study was >10%, Keverprazan 20 mg qd ranked best with a surface under the cumulative ranking curve (SUCRA) value of 84.7, followed by Ilaprazole 10 mg qd with a SUCRA value of 82.0, for the healing rate at 8 weeks. Sensitivity analysis showed that the results were robust. Subgroup analysis showed that most P-CABs had higher healing rates than PPIs, particularly for patients with severe EE. And the healing rate of Keverprazan 20 mg qd at 8 weeks ranked best in the subgroup without or with severe EE at baseline. This study showed that an 8-week treatment seemed more effective than the 4-week treatment for healing EE patients. The healing effect of Keverprazan (20 mg qd) ranked best in 8-week treatment, for both severe and non-severe EE patients. The study protocol was registered with INPLASY (registration number INPLASY2023120053).

Role of proton pump inhibitors dosage and duration in Helicobacter pylori eradication treatment: Results from the European Registry on H. pylori management.

Management of Helicobacter pylori (H. pylori) infection requires co-treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful eradication. To evaluate the role of dosage of PPIs and the duration of therapy in the effectiveness of H. pylori eradication treatments based on the 'European Registry on Helicobacter pylori management' (Hp-EuReg). Hp-EuReg is a multicentre, prospective, non-interventionist, international registry on the routine clinical practice of H. pylori management by European gastroenterologists. All infected adult patients were systematically registered from 2013 to 2022. Overall, 36,579 patients from five countries with more than 1000 patients were analysed. Optimal (≥90%) first-line-modified intention-to-treat effectiveness was achieved with the following treatments: (1) 14-day therapies with clarithromycin-amoxicillin-bismuth and metronidazole-tetracycline-bismuth, both independently of the PPI dose prescribed; (2) All 10-day (except 10-day standard triple therapy) and 14-day therapies with high-dose PPIs; and (3) 10-day quadruple therapies with clarithromycin-amoxicillin-bismuth, metronidazole-tetracycline-bismuth, and clarithromycin-amoxicillin-metronidazole (sequential), all with standard-dose PPIs. In first-line treatment, optimal effectiveness was obtained with high-dose PPIs in all 14-day treatments, in 10- and 14-day bismuth quadruple therapies and in 10-day sequential with standard-dose PPIs. Optimal second-line effectiveness was achieved with (1) metronidazole-tetracycline-bismuth quadruple therapy for 14- and 10days with standard and high-dose PPIs, respectively; and (2) levofloxacin-amoxicillin triple therapy for 14days with high-dose PPIs. None of the 7-day therapies in both treatment lines achieved optimal effectiveness. We recommend, in first-line treatment, the use of high-dose PPIs in 14-day triple therapy and in 10-or 14-day quadruple concomitant therapy in first-line treatment, while standard-dose PPIs would be sufficient in 10-day bismuth quadruple therapies. On the other hand, in second-line treatment, high-dose PPIs would be more beneficial in 14-day triple therapy with levofloxacin and amoxicillin or in 10-day bismuth quadruple therapy either as a three-in-one single capsule or in the traditional scheme.

Efficacy and Safety of Potassium-Competitive Acid Blockers Versus Proton Pump Inhibitors as Helicobacter pylori Eradication Therapy: A Meta-Analysis of Randomized Clinical Trials.

Helicobacter pylori is a gram-negative bacterium that chronically infects the gastric epithelium.Potassium-competitive acid blockers (P-CABs) are a promising alternative, being more potent than standard proton pump inhibitors (PPIs). The meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria were randomized controlled trials (RCTs) comparing P-CAB and PPI-based therapy, confirmed H. pylori infection, and measured eradication rates after at least four weeks. Subgroup analyses were conducted based on therapy type and trial location. Quality assessment used the Cochrane risk-of-bias tool, RoB 2.0, and statistical analysis was performed using ReviewManager (RevMan) 5.4 (2020; The Cochrane Collaboration,London, United Kingdom). A p-value of <0.05 is considered statistically significant. In the intention-to-treat (ITT) analysis, P-CABs demonstrated superior overall efficacy, consistently observed in the first-line treatment subgroup. However, no significant difference was found in the subgroup receiving salvage therapy. Another ITT subgroup analyzed the impact of geographical location, favoring P-CABs in the overall study population and the Japanese subgroup. However, no statistically significant differences were found in the subgroups of other countries. In the PPA, P-CABs showed superior efficacy overall, consistently seen in the first-line treatment subgroup. However, no significant difference was found in the subgroup receiving salvage eradication therapy. Another PPA subgroup analysis considered the geographical impact on eradication rates, revealing P-CABs as superior to PPIs in the overall study population and the Japanese subgroup, but not in other countries. No significant adverse event outcomes were observed. P-CAB-based triple therapy is more effective than PPI-based triple therapy as the primary treatment for H. pylori eradication, particularly in Japanese patients. Nevertheless, regarding salvage therapy, both treatments show comparable efficacy. Additionally, the tolerability of P-CAB-based and PPI-based triple therapy is similar, with a similar occurrence of adverse events.

On-demand Versus Continuous Maintenance Treatment With a Proton Pump Inhibitor for Mild Gastroesophageal Reflux Disease: A Prospective Randomized Multicenter Study.

It remains unclear which maintenance treatment modality is most appropriate for mild gastroesophageal reflux disease (GERD). We aimed to compare on-demand treatment with continuous treatment using a proton pump inhibitor (PPI) in the maintenance treatment for patients with non-erosive GERD or mild erosive esophagitis. Patients whose GERD symptoms improved after 4 weeks of standard dose PPI treatment were prospectively enrolled at 25 hospitals. Subsequently, the enrolled patients were randomly assigned to either an on-demand or a continuous maintenance treatment group, and followed in an 8-week interval for up to 24 weeks. A total of 304 patients were randomized to maintenance treatment (continuous, n = 151 vs on-demand, n = 153). The primary outcome, the overall proportion of unwillingness to continue the assigned maintenance treatment modality, failed to confirm the non-inferiority of on-demand treatment (45.9%) compared to continuous treatment (36.1%). Compared with the on-demand group, the GERD symptom and health-related quality of life scores significantly more improved and the overall satisfaction score was significantly higher in the continuous treatment group, particularly at week 8 and week 16 of maintenance treatment. Work impairment scores were not different in the 2 groups, but the prescription cost was less in the on-demand group. Serum gastrin levels significantly elevated in the continuous treatment group, but not in the on-demand group. Continuous treatment seems to be more appropriate for the initial maintenance treatment of non-erosive GERD or mild erosive esophagitis than on-demand treatment. Stepping down to on-demand treatment needs to be considered after a sufficient period of continuous treatment.

Bismuth quadruple three-in-one single capsule three times a day increases effectiveness compared with the usual four times a day schedule: results from the European Registry on Helicobacter pylori Management (Hp-EuReg)

BackgroundThe recommended schedule for single capsule bismuth quadruple therapy (scBQT, Pylera) includes a proton pump inhibitor (PPI) two times a day and three scBQT capsules four times a day. Four...

Esophagoprotective therapy in patients with erosive esophagitis

To evaluate the advantages of using combined therapy of proton-pump inhibitors (PPIs) and esophagoprotector in comparison with basic therapy of PPIs for 4 weeks based on the results of changes in the endoscopic picture.To compare the effectiveness of 4-week PPI therapy and 4-week combination therapy with PPI and esophagoprotector Alfasoxx (sodium hyaluronate, chondroitin sulfate, poloxomer 407) in patients with erosive esophagitis (EE) of any degree according to the Los Angeles Endoscopic Classification. 81 patients with EE AC according to the Los Angeles endoscopic classification (1994) was enrolled in the study on the basis of the clinic of Peter the Great, Mechnikov North-Western State Medical University. By computer randomization, patients were divided into the control group 40 patients (pantoprazole 40 mg 1 time per day) and the intervention group 41 patients (pantoprazole 40 mg 1 time per day + Alfasoxx 1 sachet qid). The therapy was carried out for 4 weeks. In all patients before and after therapy, the frequency and severity of the main symptoms of gastroesophageal reflux disease (GERD) were assessed, esophagogastroduodenoscopy was performed. The advantage of combination therapy over standard PPI monotherapy in patients with EE was revealed. According to the results of the control endoscopy, healing of erosions of the esophageal mucosa was observed in 39 out of 41 (95.1%) patients in the intervention group and 32 out of 39 (82.1%) in the control group. The proportion of patients who showed an improvement in the endoscopic picture before and after treatment for 4 weeks by at least 1 level according to the Los Angeles classification was significantly higher in the comparison group 41 patients (100%), while in the control group 33 patients (85%); p0.009. After treatment, the combination therapy group had a lower incidence (p0.01) and severity of heartburn (p0.01). The same results are demonstrated by combination therapy regarding the symptom belching of air: in the study group after treatment, this symptom occurred less frequently (p=0.014), its severity was significantly less than in the control group (p0.01). There was a statistically significant decrease in the need for on-demand antacid therapy in the study group. In this study involving 81 patients with erosive GERD, the benefits of combination therapy were demonstrated. The addition of Alfasoxx medical device to PPI therapy increases the clinical and endoscopic efficacy of therapy. This positive effect is associated with the esophagoprotective properties of the drug, based on unique pharmacodynamic characteristics. Combination therapy for GERD is preferred in patients with EE. Studies have shown the expediency of using Alfasoxx in case of insufficient effectiveness of classical acid-suppressive therapy for GERD.

Efficacy of an esophageal mucosal protectant in the treatment of patients with gastroesophageal reflux disease: a systematic review

Gastroesophageal reflux disease (GERD) is one of the most widespread gastrointestinal pathologies and the most common reason for seeking medical care at the level of a primary link of public health services in many countries around the world. The classic clinical presentations of GERD are heartburn, belching, and regurgitation (spitting up), but the overall spectrum of GERD symptoms is broader and more heterogeneous in scope, including extraesophageal symptoms. Clinical and/or endoscopic refractoriness of some patients to the standard proton pump inhibitors (PPIs) therapy remains a global challenge in the management of patients with GERD at the current stage of clinical medicine development. A medicinal product of a fundamentally new class was developed to optimize the treatment of patients with GERD – an esophageal mucosal protectant, which consists of a fixed combination of hyaluronic acid and chondroitin sulfate dissolved in a bioadhesive carrier (polymerase 407). This review is primarily aimed at systematizing data on the efficacy of the esophageal mucosal protectant in the treatment of patients with GERD. The systematic review that summarized the results of 10 studies involving 1090 patients with GERD showed that adding this esophageal mucosal protectant to the PPI therapy increased the efficacy of GERD therapy, as well as improved the frequency of symptomatic, endoscopic and morphological response to the treatment. Such combination therapy contributes to the optimization of the treatment of patients with various disease phenotypes, regress of both esophageal and extraesophageal symptoms, and potentiation of repair of the esophageal mucosa. To increase the efficacy of treatment and improve the prognosis of the disease, this approach should be implemented at the early stages of therapy in real clinical practice.

Ellagic Acid Induces in vitro Alkalinisation of the Digestive Vacuole in Drug-Sensitive Plasmodium falciparum Strain.

BackgroundMalaria is one of the leading causes of death worldwide caused by parasites of the genus Plasmodium. The reduced efficacy of the mainstay antimalarial drugs due to the widespread of drug-resistant Plasmodium falciparum (P. falciparum) necessitates an effort to develop novel antimalarial drugs with new targets. The effects of a phenolic compound, ellagic acid, against the malaria parasite have previously been reported. This present study aimed to evaluate the effect of ellagic acid on pH of the P. falciparum digestive vacuole.MethodsThe antimalarial potential of ellagic acid against the chloroquine-sensitive strain (3D7) of P. falciparum was assessed by using a malarial SYBR Green 1 fluorescence-based (MSF) assay. The effect of different concentrations of ellagic acid on the pH of the parasite’s digestive vacuole at mid-trophozoite stage was examined by using a ratiometric pH indicator, fluorescein isothiocyanate (FITC)-dextran on the flow cytometry.ResultsThe result of the MSF assay showed that ellagic acid has an antimalarial activity (half-maximal inhibitory concentration [IC50] = 1.85 ± 4.57 nM) at par with a standard drug, artemisinin (IC50 = 1.91 ± 5.41 nM). The pH of the digestive vacuole of ellagic acid-treated parasites was significantly changed (pH values ranged from 6.11 to 6.74) in a concentration-dependent manner as compared to untreated parasites (P < 0.001). A similar effect was shown by the parasites treated with a standard proton pump inhibitor, concanamycin A.ConclusionThese findings suggest that ellagic acid might have altered the digestive vacuole pH through the inhibition of proton pumps that regulate the acidification of this organelle. Overall, this study provides a valuable insight into the potential of ellagic acid as a promising antimalarial candidate with a novel mechanism of action.

Vonoprazan: A systematic review of an alternative to proton pump inhibitors

Vonoprazan is a novel potassium-competitive acid blocker (P-CAB) that works through a reversible potassium-specific competitive mechanism to inhibit active proton pumps directly. In contrast to standard proton pump inhibitors, vonoprazan does not require acid activation or any time constraints for its administration. As a result of its rapid onset and prolonged action, vonoprazan is a suitable option for PPI. In this study, we compare the efficacy of vonoprazan and PPIs in treating Gastroesophageal Reflux Disease (GERD), H. pylori, and post-endoscopic submucosal dissection (ESD) bleeding and ulcers. A PRISMA-guided systematic review was conducted on Pubmed. It included English or Portuguese articles published in the last five years describing adult patients treated with vonoprazan and/or PPI for GERD, H. pylori, or post-endoscopic dissection of the gastroesophageal submucosa bleeding and ulcers. There were six articles on GERD. Half suggested vonoprazan was superior to PPIs, while the other half considered it non-inferior or of comparable efficacy. There were 19 articles on H. pylori eradication, and vonoprazan outperformed PPI in 68,42% (13/19) of them. Vonoprazan was more effective than PPIs in 8 of the 13 studies chosen for post-ESD and ulcer prevention. As a result, in most studies, vonoprazan is either superior or not inferior to PPIs. However, the racial bias of the results is a significant limitation, as many of these studies were conducted in the Japanese population. More research on greater racial diversity is required. Nonetheless, in the current scenario, vonoprazan is a potential alternative pharmacological treatment for post-ESD bleeding and ulcers, GERD, and H. pylori.

Evidence-based treatments for eosinophilic esophagitis: insights for the clinician.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder characterized by symptoms of esophageal dysfunction and eosinophil-predominant inflammation. Left untreated, EoE progresses to fibrous remodeling and stricture formation that impairs quality of life. Therefore, EoE requires either repeated treatments or maintenance therapy. Current guidelines recommend swallowed topical corticosteroids (STCs), proton-pump inhibitors (PPIs), or dietary intervention as initial options to induce and maintain long-term disease remission. Impractical exclusive elemental diets and suboptimal allergy testing-directed food avoidance paved the way for empirical elimination diets. These are moderately effective and highly reproducible in inducing EoE remission and allow for identification of specific food triggers. Step-up strategies, including two- and four-food rather than six-food elimination diets, should be considered as initial approaches for dietary treatment in patients of all ages, as they reduce the need for endoscopic procedures, shorten diagnostic processing time, and avoid unnecessary restrictions. Formulations of STC originally designed for asthma therapy are suboptimal for EoE treatment, with new effervescent orodispersible tablets and viscose formulations designed to coat the esophageal mucosa providing increased effectiveness at reduced doses. The anti-inflammatory effects of PPI in EoE are independent from gastric acid secretion inhibition; despite evidence from observational research, PPIs are the most commonly prescribed first-line therapy for EoE due to their accessibility, low cost, and safety profile. Double doses of PPI only induce remission in half of EoE patients, irrespective of the drug used or patients’ age. Inflammatory rather than stricturing EoE phenotype and treatment duration up to 12 weeks increase chances of achieving EoE remission. Most responders effectively maintain long-term remission with standard PPI doses. Finally, endoscopic dilation should be considered in patients with reduced esophageal caliber or persistent dysphagia despite histological remission. This article provides a state-of-the-art review and updated discussion of current therapies and newly developed options for EoE.

Itopride in treatment of laryngopharyngeal symptoms of gastroesophageal reflux disease.

In everyday otolaryngological and gastroenterological practice, the diagnosis and treatment of extraesophageal forms of gastroesophageal reflux disease are often challenging. It is sometimes the case that treatment ordered by other specialists proves ineffective or even worsens the symptoms. There is no golden standard of diagnosis for otolaryngological forms of GERD, and currently used tools (gastroscopy, laryngoscopy, impedance and pH testing) have low sensitivity and specificity. After finishing a course of successful treatment, the patients often come back to our offices with the very same symptoms. In order to improve the efficacy of treatment, a prokinetic agent can be added to the standard proton pump inhibitor therapy.

The impact of tightened prescribing restrictions on proton pump inhibitor use in Australia: An evaluation using interrupted time series analysis.

In May 2019, Australia's Pharmaceutical Benefits Scheme (PBS) tightened the prescribing restrictions for publicly subsidized high and standard strength proton-pump inhibitors (PPIs). We aimed to determine the impacts on PPI use in Australia. Population-based interrupted time series analysis of PBS dispensing claims for a 10% sample of PBS-eligible Australian residents from January 2017 to December 2020 and national prescription and over-the-counter sales to pharmacies from January 2017 to October 2020. We examined trends in monthly PPI dispensings, switches from higher to lower strength formulations, and volume (kg) dispensed and sold. From May 2019, we observed a small, immediate decrease (-7830 [95%CI: -8818 to -6842]) in standard strength PPI dispensings/month, which rebounded to exceed pre-intervention levels by December 2020. High strength dispensings decreased until the end of the study period to less than half their pre-intervention average/month; low strength dispensings/month increased until the end of the study period to more than double their pre-intervention average/month. We observed transient increases in switches to lower strength formulations post-intervention. The kilograms of PPIs sold/month followed a similar pattern to PBS kilograms dispensed/month with the exception of standard strength formulations where PBS dispensings decreased by -74 (95%CI: -93 to -55) but total sales remained unchanged (comprising PBS and private prescriptions, and over-the-counter sales). Tightened prescribing restrictions had an immediate and sustained impact on PPI use in Australia, with decreased high strength use and increased low strength use. Some patients likely switched to private market prescriptions for standard strength PPI, given the observed patterns in total volume sold/dispensed.

Effect of Food and Dosing Regimen on Safety and Efficacy of Proton Pump Inhibitors Therapy—A Literature Review

Proton pump inhibitors (PPIs) are the first-choice drugs used to prevent and treat acid-related diseases. However, a lack of satisfactory response to the standard PPI dose (“PPI failure”) is often reported, especially in patients with gastroesophageal reflux disease. Poor compliance seems to be one of the main causes of PPI failure; hence, it is crucial to gain knowledge on how to properly administer PPIs. In this review, we aimed to evaluate the effect of food, beverages, and dosing regimen on pharmacokinetics and pharmacodynamics of PPIs and to frame recommendations for healthcare professionals to improve both patient’s counseling and compliance to treatment with PPIs. A total of 201 papers were identified following a literature search. After full-text evaluation, 64 studies were included in the review. Co-administration of PPIs with a meal may affect both their bioavailability and effectiveness; however, the influence of food depends on the type of drug and its formulation. Except for pantoprazole, PPIs can be administered in the morning or evening; however, morning intake generally provides better daytime control of gastric acidity. In most cases, the choice of the proper schedule of administration should be based on the patient’s symptoms and individual dosing preferences.

High- versus low-dose proton pump inhibitors post endoscopic hemostasis in hemodialysis cases with peptic ulcer bleeding.

Post-endoscopic hemostasis treatment is not adequately addressed in high-risk patients on regular hemodialysis (HD) with emergency peptic ulcer bleeding. This study aimed to compare post-endoscopic high- versus low-dose proton pump inhibitors (PPIs) for peptic ulcer bleeding in patients undergoing regular HD. This prospective study comprised 200 patients on regular hemodialysis having emergency peptic ulcer bleeding confirmed at endoscopy and managed with endoscopic hemostasis. Half of the patients received high-dose intensive regimen and the other half received the standard regimen. Patients who were suspected to have recurrent bleeding underwent a second endoscopy for bleeding control. The primary outcome measure was rate of recurrent bleeding during period of hospitalization that was detected through second endoscopy. Rebleeding occurred in 32 patients ; 15 in the High-Dose Cohort and 17 in the Low-Dose Control (p = 0.700). No significant differences between the two dose cohorts regarding the time of rebleeding (p = 0.243), endoscopic hemostasis mode (p = 1.000), and need for surgery (p = 0.306). The highdose regimen Inhospital mortality in high-dose group was 9.0% compared to 8.0% in the low-dose group (p = 0.800). Apart from the pre-hemostatic Forrest classification of ulcers, there were no significant differences between patients with re-bleeding ulcers (n=32) and those with non-rebleeding (n=168). Rebleeding was more common in class Ia, i.e. spurting bleeders (p < 0.001). Endoscopic hemostasis followed by the standard low-dose PPI regimen of 40 mg daily IV boluses is safe and effective option for bleeding peptic ulcers in the high-risk patients under regular hemodialysis.

Different dose of new generation proton pump inhibitors for the treatment of Helicobacter pylori infection: A meta-analysis.

The evidence on whether high-dose new generation proton pump inhibitors (PPIs) including rabeprazole and esomeprazole achieve a higher eradication rate of Helicobacter pylori has not been assessed. The primary comparison was eradication and adverse events (AEs) rate of standard (esomeprazole 20 mg bid, rabeprazole 10 mg bid) versus high-dose (esomeprazole 40 mg bid, rabeprazole 20 mg bid) PPIs. Sub-analyses were performed to evaluate the eradication rate between Asians and Caucasians, clarithromycin-resistance (CAM-R) strains, and clarithromycin-sensitivity (CAM-S) strains of different dose PPIs. We conducted a literature search for randomized controlled trials comparing high-with standard-dose esomeprazole and rabeprazole for H. pylori eradication and AEs. A total of 12 trials with 2237 patients were included. The eradication rate of high-dose PPIs was not significantly superior to standard-dose PPIs regimens: 85.3% versus 84.2%, OR 1.09 (0.86–1.37), P = 0.47. The high dose induced more AEs than those of the standard dose, but didn’t reach statistical significance (OR 1.25, 95% CI: 0.99–1.56, P = 0.06). Subgroup analysis showed that the difference in eradication rate of PPIs between high- and standard-dose groups were not statistically significant both in Asians (OR 0.99, 95% CI 0.75–1.32, P = 0.97) and Caucasians (OR 1.27, 95% CI 0.84–1.92, P = 0.26). Furthermore, there were similar eradication rates in CAM-S (OR 1.2; 95% CI 0.58–2.5; P = 0.63) and CAM-R strains (OR 1.08; 95% CI 0.45–2.56; P = 0.87) between the standard-and high-dose groups. High and standard dosages of new generation of the PPIs showed similar H. pylori eradication rates and AEs as well as between Asian versus Caucasian populations, with or without clarithromycin-resistance. However, further studies are needed to confirm.

High proton pump inhibitor exposure increases risk of calcinosis in systemic sclerosis

To investigate the association between proton pump inhibitor (PPI) use and the presence and severity of calcinosis in SSc. We analysed data from two SSc cohorts from a single centre. Cohort 1 included 199 patients reviewed over 10 years, for whom retrospective data on PPI use and calcinosis were available. Cohort 2 was recruited prospectively and included 215 consecutive patients, who underwent clinical assessment. Outcomes of interest were presence of current calcinosis (CC) or calcinosis at any time (CAT). The cohort 1 data analysis showed that among patients on standard dose PPI 20% had calcinosis, while in those on high doses of PPI calcinosis was present in 39% (P = 0.003). Analysis of the data from cohort 2 confirmed these findings, demonstrating that the odds of CAT increased significantly with longer PPI exposure [odds ratio (OR) 1.04, 95% CI: 1.02, 1.06; P < 0.001], longer disease duration (OR 1.08, 95% CI: 1.05, 1.12; P < 0.001) and greater age (OR 1.03, CI: 1.01, 1.05; P = 0.010). Multivariable logistic regression showed that higher exposure to PPI remained a significant predictor of calcinosis, with PPI exposure >10 years increasing the risk of CAT >6-fold, compared with no PPI (OR 6.37, 95% CI: 1.92, 21.17; P = 0.003) after adjusting for disease duration and antibodies. We confirm a significant association between high PPI exposure with severity of calcinosis in SSc. Given the clinical impact of calcinosis and reflux in SSc, PPI exposure as a potentially modifiable risk factor for calcinosis requires further evaluation.

Impact of NPS MedicineWise general practitioner education programs and Choosing Wisely Australia recommendations on prescribing of proton pump inhibitors in Australia

BackgroundThis study evaluated the impact of multifaceted NPS MedicineWise programs that targeted all general practitioners (GPs) in Australia in 2009 and 2015 with the aim of reducing unnecessary prescribing of proton pump inhibitors (PPIs) and encouraged stepping down to a lower strength PPI or to discontinue treatment. The 2015 intervention coincided with the release of Choosing Wisely Australia recommendations from the Royal Australian College of General Practitioners (RACGP).MethodsOutcome measures included monthly dispensing rates of different strength PPIs prescribed by GPs to concessional patients in Australia. All PPIs were categorized according to the May 2019 revised classifications for standard and low strength PPIs except for esomeprazole 40 mg which was classified as a standard strength and esomeprazole 20 mg as low strength for this analysis. Time series analyses was conducted of the dispensing rates of PPI prescriptions for concessional patients between January 2006 and June 2016 using the Pharmaceutical Benefits Scheme (PBS) and Medicare Benefits Schedule (MBS) databases in Australia. Participants were GPs with dispensed PPI prescriptions to concessional patients between January 2006 and June 2016.ResultsFollowing the 2009 NPS MedicineWise program we observed a 6.7% reduction in the expected dispensing rate of standard strength PPIs for concessional patients between April 2006 and March 2015, and an 8.6% reduction between April 2009 and June 2016 following the 2015 program launch. We observed a significant increase of 5.6% in the dispensing rate of low strength PPIs for concessional patients between April 2009 and March 2015, and no significant change in trend following the 2015 program.ConclusionsThe NPS MedicineWise programs were associated with reductions in the dispensing rate of standard strength PPIs by June 2016 and an increase in the dispensing rate of low-strength PPIs by March 2015 although this trend did not continue following the 2015 program. This suggests that GPs are stepping down patients to lower strength PPIs following the educational programs. However, lower strength PPIs are still not the majority of PPIs dispensed in Australian and regular interventions to sustain and improve PPI management by GPs may be warranted.